Signal Transduction and Protein Ph os p ho ry I at ion

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Signal Transduction and Protein Phosphorylation Edited by

L. M. G. Heilmeyer Institute for Physiological Chemistry I Ruhr University-Bochum Bochum, Federal Republic of Germany

Plenum Press New York and London Published in cooperation with NATO Scientific Affairs Division

Proceedings of a NATO/FEBS Summer School on Signal Transduction and Protein Phosphorylation, held September 14-26,1986, at the Korgialenios School, on the Island of Spetsai, Greece

Library of Congress Cataloging in Publication Data

NATO/FEBS Summer School on Signal Transduction and Protein Phosphoryl­ation (1986: Korgialenios School) Signal transductionand protein phosphorylation.

(NATO ASI series. Series A, Life sciences; vol. 135) "Proceedings of a NATO/FEBS Summer School on Signal Transduction and

Protein Phosphorylation, held September 14-26, 1986, at the Korgialenios School, on the Island of Spetsai, Greece"-T.p. verso.

"Published in cooperation with NATO Scientific Affairs Division." Includes bibliographies and index. 1. Phosphoproteins-Metabolism-Congresses. 2. Phosphorylation-Con­

gresses. 3. Proteins-Metabolism-Congresses. 4. Cellular control mechanism -Congresses. I. Heilmeyer, L. M. G. (Ludwig M. G.), 1937- . 11. North Atlantic Treaty Organization. Scientific Affairs Division. 111. Federation of European Biochemical Societies. IV. Title. V. Series: NATO ASI series. Series A, Life Sciences; v. 135. [DNLM: 1. Chemistry, Organic-congresses. 2. Phosphotrans­ferases-metabolism-congresses. 3. Proteins-metabolism-congresses. QU 55 N2857s 1986] QP552.P5N38 1986 599'.01'852 87-15398 ISBN 978-1-4757-0168-5 ISBN 978-1-4757-0166-1 (eBook) DOI 10.1007/978-1-4757-0166-1

© 1987 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1987 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013

All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

PREFACE

A NATO Advanced Study Institute on "Signal Transduction and Protein Phosphorylation" was held to overview recent developments in this area. The participants in the Institute dealt with protein phosphorylation as the most prevalent mode of regulation of cellular processes.

First, methods needed to analyze the complex cascade systems involved were reviewed, including protein sequencing, crystallo­graphy, characterization and isolation of membrane proteins, use of monoclonal or polyclonal antibodies and application of fluorescent probes. In great detail the x ray crystallographic structure of glycogen phosphorylase was presented. This enzyme is located at the end of a signal cascade triggered by the hormonal activation of the membrane-bound adenylate cyclase. The interaction of the hormone/receptor with the catalytic subunit of the adenylate cyclase involves GTP-binding proteins. The function of these recently detected intermembrane coupling factors were reviewed, as weIl as the structure and properties of various protein kinases.

Major emphasis was placed on Ca2+ as a second messenger, its metabolism, mechanism of release and uptake from intracellular stores and its role on cell motility and muscle contraction.

Two classes of protein phosphatases were discussed. They differ in their subunit structure and substrate specificity and are subject of a highly complex regulatory mechanism as yet not fully under­stood.

The general principles of regulation by signal transduction and protein phosphorylation/dephosphorylation were presented in the context of specific cellular processes. These included control of protein synthesis at the translational level and the mechanism of action of interferon. The discussion included the role of protein tyrosine kinases which are structurally related to some oncogene products and, therefore, implicated in various aspects of cell development and transformation.

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This text presents the content of the major lectures and important posters displayed and discussed during the Institut's program. It is the hope that inclusion of recent results discussed in the poster sessions presents the reader an impression on the forefront of research in this area. Initiating this book the editor hopes to convey the proceedings ofthe NATO Advanced Study Institute on "Signal Transduction and Protein Phosphorylation" to a larger audience and to offer a comprehensive ac count of those developments in an area which is growing very fast.

Ludwig Heilmeyer

Bochum, February 1987

CONTENTS

I. REGULATORY PROPERTIES OF SIGNAL CASCADES

PROTEIN PHOSPHORYLATION. A HISTORICAL OVERVIEW •••••••••••••••••• 3 E.H. Fischer

SIGNAL TRANSDUCTION THROUGH cAMP AND cGMP J.D. Corbin, S.J. Beebe, C.E. Cobb, S.H. Francis, J.N. Wells, S.L. Keely, T.W. Gettys, P.F. Blackmore, L. Wolfe and L.R. Landiss

SIGNAL CASCADES IN REGULATION OF GLYCOGENOLYSIS L.M.G. Heilmeyer, Jr.

THE ROLE OF ZERO-ORDER ULTRASENSITIVITY AMPLIFICATION IN THE REGULATION OF THE GLYCOGEN PHOSPHORYLASE A -

11

17

PHOSPHORYLASE B CYCLE .•...••••.•••••.••....•..••...•..•.••.•• 31 R.D. Edstrom, J.S. Bishop and M.H. Meinke

PROTEIN SEQUENCING AND COVALENT PROCESSING K.A. Walsh

PROTEIN CRYSTALLOGRAPHY D.I. Stuart

SIGNAL TRANSDUCTION BY THE ADENYLATE CYCLASE SYSTEM K.R. Jakobs, P. Gierschik, R. Grandt, R. Marquetant and R. Strasser

PROTEIN PHOSPRORYLATION/DEPHOSPHORYLATION AND REVERSIBLE PHOSPHORYLATION BINDING IN

37

45

55

RRABDOMERIC PHOTORECEPTORS ••••••••••••••••••••••••••••••••••• 65 J. Bentrop and R. Paulsen

UTILIZATION OF A MONOCLONAL ANTIBODY TO STUDY IN VITRO PROSPHORYLATION OF A LOW Km PHOSPHODIESTERASE ~........... 71 D.H. Reifsnyder, S. A. Harrison, C.H. ~~cphee and J.A. Beavo

SENSITIVITY OF A cAMP PDE TO ROLIPRAM IN DIFFERENT ORGANS H.H. Schneider, G. Pahlke and R. Schmiechen

IMMUNOLOCALIZATION OF PROTEINS IN SITU BY LIGHT AND

81

ELECTRON I1ICROSCOPY ••••••••••••••••••.••••••••••••••••••••••• 87 U. Gröschel-Stewart

FLUORENCENT PROBES •••••••••••••••••••••••••••••••••••••••••••••• 93 N. Selve, E. Schröer, K. Ruhnau and A. Wegner

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BINDING OF FLUORESCENT ANALOGS OF CYCLIC GMP TO EPENDENT cGMP-DEPENDENT PROTIN KINASE................................. 99 H.H. Ruf, M. Rack, W. Landgraf and F. Hofmann

11. REGULATION OF MUSCLE CONTRACTION

REGULATION OF ACTOMYOSIN ATPASE ••••••••••••••••••••••••••••••• 107 E.W. Taylor

REGULATION OF MUSCLE CONTRACTION •••••••••••••••••••••••••••••• 115 S. V. Perry

DETERMINATION OF PHOSPHATES IN CARDIAC TROPONIN BY PHOSPHATE ANALYSIS AND PHOSPHOSERINE MODIFICATION ••••••••••••••••••••••• 121

K. Swiderek, K. Jaquet, H. E. Meyer, L.M.G. Heilmeyer, Jr.

MYOSIN LIGHT CRAIN KINASE ••••••••••••••••••••••••••••••••••••• 127 S. V. Perry

CONTRACTLlLE PROTEIN ISOFORMS U. Gröschel-Stewart

135

ACTIN-POLYMERIZATION •••••..•.•••••.••••••••••.••••.•.•.•••.••• 141 E. Schröer, K. Ruhnau, N. Selve and A. Wegner

ADP-RIBOSYLATION OF ACTIN BY BOTULINUM C2 TOXIN ••••••••••••••• 149 K. Aktories, M. Bärmann, M. Laux, K.H. Reuner, P. Presek and B. Schering

ACTIN-BINDING PROTEINS •••••••••••••••••••••••••••••••••••••••• 155 K. Ruhnau, N. Selve, E. Schröer and A. Wegner

MODULATION OF CARDIAC Ca CHANNELS BY PHOSPHORYLATION W. Trautwein

REGULATION OF THE Ca-CHANNEL BY PHOSPHORYLATION-

161

DEPHOSPHORYLATION •••••••••••••••••••••••••••••••••••••••••• 177 J. Hesche1er, M. Kameyama, W. Trautwein, G. Mieskes, F. Hofmann

111. STRUCTURE FUNCTION RELATIONSHIP OF CASCADE ENZYMES

THE PROTEIN KINASE FAMILY ••••••••••••••••••••••••••••••••••••••• 185 K.A. Walsh

PRO TEIN KINASE C OF INTESTINAL EPITHELIUM: ITS ROLE IN THE CONTROL OF IONIC TRANSPORT P.L. Lazo and G. Velasco

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PROSTAGLANDIN E - AND SODIUM NITROPRUSSIDE-REGULATED PROTEIN PHOSPHORYLATION IN PLATELETS ••••••••••••••••••••••••• 201 M. Nieberding, R. Waldmann and U. Walter

STRUCTURE, FUNCTION AND REGULATION OF PROTEIN PHOSPHATASE E.H. Fischer, S. McNall and N. Tonks

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207

HIGH MOLECULAR WEIGHT PHOSPHORYLASE PHOSPHATASE FROM MUSCLE GLYCOGEN PARTICLES •••••••••••••••••••••••••••••••••••• 219 E. Villa-Moruzzi

SUBCELLULAR DISTRIBUTION AND CHARACTERISTICS OF HEPATIC PRO TEIN PHOSPHATASE ACTING ON GLYCOGEN PHOSPHORYLASE AND ON GLYCOGEN SYNTHASE ••••••••••••••••••••••••••••••••••••• 225 M. Bollen, J. Vandenheede, J. Goris and W. Stalmans

ACUTE HORMONAL REGULATION OF LIPLYSIS AND STEROlDOGENESIS ••••••••••••••••••.••••••••••••••••••••••••••• 321 S.J. Yeaman, S.R. Cordle, R.J. Colbran, A.J. Garton and R.C. Honnor

THE ROLE OF PHOSPHORYLATION IN THE REGULATION OF ACETYL­CoA CARBOXYLASE ACTIVITY BY INSULIN AND OTHER HORMONES A.C. Borthwick

239

GLYCOGEN METABOLISM IN SMOTH MUSCLE ••••••••••••••••••••••••••••• 243 T.G. Sotiroudis, S. Nikolaropoulos and A.E. Evangelopoulos

THE SITES OF INTERACTION OF CALMODULIN WITH PHOSPHO-FRUCTOKINASE •••••••••••.•••••••••••••••••••.••••..•••..•.•••• 259 B. Buschmeier, H.E. Meyer, H.-H. Kiltz, L.M.G. Heilmeyer, jr. and G.W. Mayr

PHOSPHORYLATION SITES ON TYROSINE HYDROXYLASE P.R. Vuilliet and D.G. Hardie

IV. CONTROL OF CELLULAR PROCESSES

REGULATION OF AMINO ACIDS - BIOSYNTHESIS IN PROKARYOTES G.N. Cohen

DESENSITAZION OF GLUCAGON-STIMULATED ADENYLATE CYCLASE IS MEDIA TED BY STIMULATION OF INOSITOL PHOSPHOLIPID

265

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METABOLISM ••••••••••••••••••••••••••••••••••••••••••••••••••• ,28'9 G.J. Murphy, M.J.O. Wakelam and M.D. Housley

PHOSPHOINOSITIDE-HYDROLYSIS IN A STIMULATED MURINE T CELL CLONE •••••••••••••••••••••••••••••••••••••••••• 293 B. Behl, B. Schwinzer and K. Resch

PHOSPHORYLATION OF TWO DIFFERENT FORMS OF THE CYTOSKELETAL PROTEIN CALDESMON BY PROTEIN KINASE C ••••••••••••••••••••••••• 299 D.W. Litchfield and E.H. Ball

GUANINE NUCLEOTIDE REGULATORY PROTEIN COUPLES ANGIOTENSIN 11 RECEPTORS TO PHOSPHOLIPASE C IN MESANGIAL CELLS ••••••••••••••••••••••••••••••••••••••••••• 305 J. Pfeilschifter

METABOLISM OF PHOSPHATIDYLINOSITIDES IN RETICULOYTES -ISOPROTERENOL AFFECTS THE TURNOVER OF POLYPHOSPHOINOSITIDES 311 D. Maretzki, B. Reimann, E. Schwarzer, M. Kostic and S. Rapoport

ROLE ~f CYTOPLASMIC pH FOR STIMULUS-INDUCED CA MOBILIZATION IN HUMAN PLATELETS ••••••••••••••••••••••• 317 W. Siffert, P. Scheid and J.W.N. Akkerman

PHOSPHATIDYLINOSITOL PHOSPHORYLATION IN FAST SKELETAL MUSLCE MlliBRANES ••••••••••••••••••••••••••••••••••••••••••••• 32.3 G. Behle, M. Varsanyi, R. Thieleczek and L.M.G. Heilmeyer, Jr.

THE ROLE OF PHOSPHORYLATION IN GROWTH CONTROL AND MALIGANT TRANSFORMATION .••••••••••••.••••••••.••.•••••••..••• 329 Tony Hunter

THE EFFECTS OF BOTULINUM NEUROTOXIN AND TETRODOTOXIN ON PRO TEIN PHOSPHORYLATION IN PURE CHOLINERGIC SYNAPTOSOMES ••••••••••••••• 345 X. Guitart, J. Marsal and C. Solsona

PROTEIN PHOSPHORYLATION IN MEMBRANES OF NICOTIANA TABACUM K. Palme, J. Mayer and J. Schell

INTERLEUKIN 1 INDUCES TYROSINE PHOSPHORYLATION IN PLASMA

351

MEMBRANES OF THE TUMOR CELL LINES K 562 AND BW 5147 357 M. Martin, U. Kyas and K. Resch

THE REGULATION OF cAMP-DEPENDENT PROTEIN KINASES IN NORMAL AND TRANSFORMED L6 MYOBLASTS ••••••••••••••••••••••••• 363 I.A.J. Lorimer and B.D. Sanwal

PROTEIN PHOSPHORYLATION IN RESPONSE TO DIVERSE MITOGENIC AGENTS IN DOG THYROID CELLS ••••••••••••••••••••••••••••••••• 369 L. Contor, F. Lamy, R. Lecocq and J.E. Dumont

CONTROL OF PROTEIN SYNTHESIS INITIATION FACTOR eIF-2a PHOSPHORYLATION BY INTERFERON ••••••••••••••••••••••• 375 G. Thomas

GROWTH FACTIOR-MEDIATED ACTIVATION OF S6 PHOSPHORYLATION AND PROTEIN SYNTHESIS •.••••••.••••••••••••••••.••.•.•••••••. 383 G. Thomas

INACTIVATION OF AN S6 KINASE BY PROTEIN PHOSPHATASES L.M. Ballou, P.JenÖ and G. Thomas

391

INDEX.................................. .. .... .. ...•.... ...... .. 397

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